Stabilization of bilirubin in control sera and calibrators

Abstract

The invention concerns a stable control serum or calibration serum containing bilirubin to analytically examine the methodical accuracy of individual parameters in human sera or patients. The control serum or calibration serum according to the invention is used to stabilize bilirubin in solutions and to generally increase the stability of control sera or calibration sera.

We claim: 
     
       1. Control serum or calibration serum comprising bilirubin and a stabilizer comprising at least one compound selected from the group consisting of: a compound of formula (I): ##STR3##  wherein R 1  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ; R 2  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ;   R 3  is H or OH;   R 4  is H, COOR 5 , COR 5  or SO 3  R 5     R 5  is H or C 1-6  alkyl;     and a compound of formula (II) ##STR4##  wherein R 1  is H, Halogen or C 1-6  alkyl; R2is H, C 6  alkyl, or C 1-6  alkoxy.     
     
     
       2. The control serum or calibration serum of claim 1 wherein the stabilizer comprises a compound of formula II, wherein the halogen is selected from the group consisting of Cl, Br, and F. 
     
     
       3. The control serum or calibration serum of claim 1 wherein the stabilizer comprises a compound of formula (1) wherein R 1  is OH, R 2  is OH, R 3  is H, and R 4  is COOC 3  H 7  ; or wherein R 1  is OH, R 2  is H, R 3  is OH, and R 4  is COC 4  H 9  (2,4,5-trithydroxybutyrophenone). 
     
     
       4. The control serum or calibration serum of claim 1, wherein the stabilizer comprises a compound of formula II, wherein the compound of formula (II) is a compound wherein R 1  is H and R 2  is CH 3  (1-(4-methylphenyl)-semicarbazide). 
     
     
       5. The control serum or calibration serum of claim 1, further comprising preservatives or analyte stabilizers. 
     
     
       6. The control serum or calibration serum of claim 1 which is stored under protective gas. 
     
     
       7. The control serum or calibration serum claim 1, comprising 0.001 to 1.5 mmol/l of at least one compound of formula (I) or formula (II). 
     
     
       8. A method for measuring bilirubin comprising: a) measuring bilirubin in a sample,   b) measuring bilirubin in the control serum or calibration serum according to claim 1,   c) determining a content of bilirubin in said sample by comparing the measurement determined in step a) with the measurement determined in step b).   
     
     
       9. In a kit for measuring bilirubin in a biological sample, said kit containing reagents necessary for measuring bilirubin, the improvement comprising: a separate package containing the control serum or calibration serum containing bilirubin according to claim 1. 
     
     
       10. The control or calibration serum of claim 1, further comprising preservatives and analyte stabilizers. 
     
     
       11. The control or calibration serum of claim 1, comprising 0.001 to 1.5 mmol/l of at least one compound of formula (I) and formula (II). 
     
     
       12. A process for the stabilization of a control serum or calibration serum containing bilirubin, said process comprising adding at least one compound selected from the group consisting of: a compound of formula (I) and a compound of formula (II) to a control serum or calibration serum containing bilirubin, wherein a compound of formula (I) is ##STR5##  wherein R 1  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ; R 2  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ;   R 3  is or OH;   R 4  is H, COOR 5 , COR 5  or SO 3  R 5     R 5  is H or C 1-6 , alkyl;     and a compound of formula (II) is ##STR6##  wherein R 1  is H, Halogen or C 1-6  alkyl; R 2  is H, C 1-6  alkyl , or C 1-6  alkoxy.     
     
     
       13. A method for increasing the storage stability of control sera or calibration sera comprising bilirubin, comprising adding at least one compound selected from the group consisting of a compound of formula (I) and a compound of formula (II) to the control sera or calibration sera, wherein a compound of formula (I) is ##STR7## wherein R 1  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ; R 2  is H, OH, C 1-8  alkyl, COOR 5  or SO 3  R 5  ;   R 3  is H or OH;   R 4  is H, COOR 5 , COR 5  or SO 3  R 5     R 5  is H or C 1-6  alkyl;   and a compound of formula (II) is ##STR8##  wherein R 1  is H, Halogen or C 1-6  alkyl; R 2  is H, C 1-6  alkyl, or C 1-6  alkoxy.